a) We have continued to enroll depressed patients with Bipolar Mood Disorder in our idazoxan treatment protocol at Friends Hospital, PA. Analyses of clinical responses of patients treated to date confirm our earlier findings. Idazoxan appears to have a sustained antidepressant effect and patients with bipolar mood disorder are much more likely to respond than those with unipolar depression. Approximately 60% of patients with bipolar depression experienced a 50% or greater reduction in depressive symptoms while taking at least 80 mg of idazoxan a day (divided). Since Dr. Potter's retirement, no further patients have been enrolled at NIMH and the protocol is being kept active to permit completion of the sample at Friends Hospital and provide medication to those patients identified as "responders". b) Our findings in healthy volunteers (MH-01850-10) provide evidence that imaging the metabolic effects of idazoxan is sensitive to functional differences in response to alpha-2 blockade. A sample of patients treated with ECT had FDG PET studies including an idazoxan challenge before and after ECT. Preliminary analyses of those data suggest that there is a slight increase in resting norepinephrine levels after ECT and consequently an increased sensitivity to alpha-2 blockade. The brain metabolic responses show parallel changes, with more widespread relative reductions in frontal cortex following idazoxan after completion of ECT. While a small sample, with the departure of Dr. Michael Henry we have ended that study and will finish analyses of the clinical and PET data.